通过数字空间图谱确定原发性子宫癌肉瘤的瘤间和瘤内异质性免疫表现

Yingxuan Li, Wei-Chou Lin, Ko-Chen Chen, Wen-Chun Chang, Chin-Jui Wu, Lin-Hung Wei, Ruby Yun-Ju Huang, Bor-Ching Sheu
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摘要

子宫癌肉瘤(UCS)是一种罕见的妇科癌症,预后不良。已知其双相组织学成分与预后有关。剖析 UCS 中肿瘤的异质性对于发现用于患者分层的分子生物标记物至关重要。本研究旨在利用空间图谱技术分析 UCS 肿瘤内不同组织学成分的免疫表现。研究纳入了 23 名 UCS 患者,对其肿瘤切片进行了 nanoString GeoMx 数字空间图谱分析(DSP),在 491 个切片中分析了 30 种免疫相关蛋白。我们确定了不同的集群标记亚型,其免疫标记表达各不相同。癌和肉瘤成分中的免疫表现存在显著差异。表明 M2 巨噬细胞(CD45+CD163+)和上皮-间质转化(EMT)(SMA、纤连蛋白)的标记物在肉瘤成分中高表达。5年内复发的患者和5年内未复发的患者在每种组织学成分中的免疫表现亚型也有所不同。中性粒细胞/PMN-MDSC标记物高表达(CD66b)的集群标记亚型与较长的生存期相关,而NK细胞标记物高表达(CD56)的亚型与较差的预后相关。我们的研究结果表明,UCS肿瘤癌成分中的免疫特征将决定患者的预后,应将其作为患者分层的一种策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Inter- and intra-tumor heterogeneous immune presentation in primary uterine carcinosarcoma determined by digital spatial profiling
Uterine carcinosarcoma (UCS) is a rare gynecologic cancer with unfavorable prognosis. Its biphasic histologic components are known to associated with outcomes. Dissecting the tumor heterogeneity within UCS is crucial to discover molecular biomarkers for patient stratification. The aim of this study was to utilize spatial profiling technology to analyze immune presentation in different histological components within UCS tumors. The study included 23 UCS patients whose tumor sections were subjected to nanoString GeoMx Digital Spatial Profiling (DSP) to profile 30 immune-related proteins in 491 segments. We identified distinct cluster-labeled subtypes showing varied immune marker expressions. The immune presentations within the carcinoma and sarcoma components showed significant differences. Markers indicating M2 macrophages (CD45+CD163+) and epithelial-mesenchymal transition (EMT) (SMA, fibronectin) were highly expressed in the sarcoma components. The immune presentation subtypes within each histological component also differed between patients with recurrence in 5 years and without recurrence over 5 years. The cluster-labeled subtype with high Neutrophil/PMN-MDSC marker expression (CD66b) was associated with longer survival, whereas the subtype with high NK cell marker expressions (CD56) was linked to poor prognosis. Our result suggested that immune features within the carcinoma component of UCS tumors would determine patient outcomes and should be considered as a strategy for patient stratification.
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